Tumor-associated antigens located at the cell surface serve as potential targets for the immune system of the host and may be important in establishing or maintaining malignant phenotype of the tumor cell. The long-term objective of the proposed research is to understand the genetic mechanisms by which the tumor cell regulates expression of its cell surface antigens. To accomplish this aim, we will study several normal and tumor-associated antigens of murine lymphomas in order to define and understand the mechanism of action of the genes which are critical in the regulation of their expression on the cell surface. The Thy-1, T200, Pgp-1 and TL glycoproteins will be analyzed in detail. Mutants which fail to express specific antigens on their cell surface will be isolated and the mutant phenotype analyzed by somatic cell genetics. Where appropriate, further studies at the protein and nucleic acid levels will be carried out to establish the molecular basis of the defect. Positive selection techniques (cell sorting) will be used to isolate revertants of these mutants and to isolate mutants which express antigens not normally expressed by the wild-type cell line. Hybrids between tumor cells representing normal cells in different states of differentiation will also be studied to gain further insight into the mechanisms regulating the expression of these cell surface antigens. We will attempt to develop nucleic acid probes for the T200 and Pgp-1 structural genes using cotransfection of the cellular genes linked to a plasmid vector and plasmid rescue as the cloning strategy.